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-  2018 

Machado-Joseph病动物模型研究进展 Research Progress on Mouse Models of Machado-Joseph Disease

Keywords: 脊髓小脑共济失调3型,Machado-Joseph病,动物模型

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Abstract:

Machado-Joseph病(MJD)又称脊髓小脑共济失调3型(SCA3),是常染色体显性遗传小脑共济失调(ADCAs)的一种,属于一类遗传性神经退行性疾病。其致病基因为MJD1(也称ATXN3)。到目前为止在颅内表达全长突变ataxin-3蛋白的MJD转基因小鼠模型已建立,本文主要对这些动物模型进行了比较。它们的主要区别在于DNA结构的不同,表现在ataxin-3亚型、多聚谷氨酰胺(polyQ)数量及转基因表达启动子的不同。大多数动物模型从体重、平衡、步态、肢体姿势、活动及死亡年龄等行为学改变进行了表型分析。病理分析主要包括小脑深部核团、脑桥、丘脑底核、黑质、脊髓小脑核团神经元及Purkinje细胞是否发生神经退行性变,并量化分析核内包涵体及神经元数量。实验室应重视利用目前已有的MJD/SCA3动物模型或制作新的动物模型从推迟疾病发生、延缓疾病进展、清除神经元核内包涵体、延长寿命等方面找到治疗新靶点

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